The primary goal of the e studies is an understanding of the short-term regulation of tyrosine hydroxylase in the central nervous system. We have previously shown an activation of the soluble enzyme (via a decrease in the apparent Km for the reduced pterin cofactor) by phosphorylation or catecholamine removal by G-25 chromatography in striatum and adrenal gland. We have extended these observations to the hypothalamus. Our major finding has been that phosphorylation results in a significant reduction in Ki for dopamine and release from end-product inhibition as its primary means of tyrosine hydroxylase activation. The data suggests that this mechanism could be operative in vivo at physiological concentrations of dopamine. BIBLIOGRAPHIC REFERENCES: Lovenberg, W., Ames, M.M. and Lerner, P.: Regulation of tyrosine hydroxylase activity. In Costa, E. and Gessa, G.L. (Eds.): Advances in Biochemical Psychopharmacology. New York, Raven Press, 1977, Vol. 16 pp. 461-464. Lerner, P., Ames, M.M. and Lovenberg, W.: The effect of EGTA and calcium on tyrosine hydroxylase activity. Molecular Pharmacology 13: 44-49, 1977.